The murine H-2K and H-2D transplantation alloantigens are cell membrane integrated glycoproteins carrying the antigenic determinants involved in tissue graft rejection and associative recognition in immune response. The molecular expression of these antigens is controlled by genes in the unusually complex and polymorphic genetic region termed the Major Histocompatibility Complex located on chromosome 17. The long-term objective of the proposed research project is to describe the molecular architecture of these membrane specific polymorphic gene products in order to understand the organization and expression of the H-2 genes as well as the structural and functional properties associated with the antigens themselves, as integral components of the plasma membrane. Our major effort has been directed towards the use of radiochemical sequencing methodology to determine the total amino acid sequence of the H-2Kb gene product. CNBr peptides have been isolated from this molecule, characterized, and aligned. Sequence analysis of the five fragments comprising the antigenically active papain cleaved molecule has been carried out. Sequence determination has also begun on the H-2Db, H-2Dd and H-2Ld molecules to obtain data for comparative purposes. Studies also have been carried out on the structure of several mutants of the H-2Kb series and of the mutant H-2D dml. Full peptide mapping studies have shown in all cases that the mutant glycoprotein is different from the parent glycoprotein. In the case of the H-2Kb series only small differences were noted as compared with the parent H-2Kb. In the case of the H-2D dml mutant larger differences were noted as compared to the parent H-2D glycoprotein.